Pergamum AB

Stockholm, Sweden

Pergamum AB

Stockholm, Sweden

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Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP.2013.1.2-2 | Award Amount: 10.45M | Year: 2013

Resistance to traditional antibiotics is a rapidly increasing problem that in a few years could make infections impossible to treat and bring the state of medical care back to the pre-antibiotic era from the beginning of the last century. Antimicrobial peptides (AMPs) have a huge potential as new therapeutics against infectious diseases as they are less prone to induce resistance due to their fast and non-specific mechanism of action. The aim of FORMAMP is to explore a number of innovative formulation and delivery strategies based on nanotechnology in order to improve the efficiency and stability of AMPs in clinical development. Functional delivery systems that can be applied directly on the infected site will be developed for treatment of infections in skin and burn wounds, as well as lung infections caused by Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and Mycobacterium tuberculosis (MTB). Formulation and delivery strategies to prevent and treat biofilm formation related to these conditions will be developed. Different nanoformulation platforms, particularly promising for peptide delivery, controlled release strategies and technologies against proteolytic degradation of peptides will be evaluated in the project. These include lipid-based systems such as lipidic nanocapsules, polymer-based structures such as dendrimers and microgels as well as nanostructured mesoporous silica. The possibility to formulate the nanostructured materials into efficient drug delivery systems such as a topical spray or gel and pulmonary aerosol will be evaluated. The effect of nanoformulated AMPs will be evaluated with state-of-the art in vitro models and in vivo models. The results of this interdisciplinary project will generate efficient treatment strategies combatting one of the largest threats to our health care system today, reducing healthcare costs and expand the growth of European enterprises within the field of pharmaceutics and nanomaterials.


Gronberg A.,Pergamum AB | Mahlapuu M.,Pergamum AB | Stahle M.,Pergamum AB | Whately-Smith C.,Pergamum AB | Rollman O.,Pergamum AB
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society | Year: 2014

Venous leg ulcers (VLUs) are one of the most prevalent types of chronic wounds. The aim of this study was to determine the safety and dose-response efficacy of the human synthetic peptide LL-37 in the treatment of hard-to-heal VLUs. This first-in-man trial included 34 participants with VLUs and comprised a 3-week, open-label, run-in period on placebo, followed by a 4-week randomized double-blind treatment phase with twice weekly applications of LL-37 (0.5, 1.6, or 3.2 mg/mL) or placebo, and a 4-week follow-up. The healing rate constants for 0.5 and 1.6 mg/mL of LL-37 were approximately six- and threefold higher than for placebo (p = 0.003 for 0.5 mg/mL and p = 0.088 for 1.6 mg/mL). Square-root transformed wound area data showed improved healing for the 0.5 and 1.6 mg/mL dose groups compared with pretreatment values (p < 0.001 and p = 0.011, respectively). Consistently, treatment with the two lower doses markedly decreased the mean ulcer area (68% for 0.5 mg/mL and 50% for 1.6 mg/mL groups). No difference in healing was observed between the groups receiving 3.2 mg/mL of LL-37 and placebo. There were no safety concerns regarding local or systemic adverse events. In conclusion, topical treatment with LL-37 for chronic leg ulcers was safe and well tolerated with the marked effect on healing predictors at the two lower doses warranting further investigations. © 2014 by the Wound Healing Society.


Myhrman E.,Pergamum AB | Hakansson J.,Pergamum AB | Lindgren K.,Pergamum AB | Bjorn C.,Pergamum AB | And 2 more authors.
Applied Microbiology and Biotechnology | Year: 2013

Dramatic increase in bacterial resistance towards conventional antibiotics emphasises the importance to identify novel, more potent antimicrobial therapies. Antimicrobial peptides (AMPs) have emerged as a promising new group to be evaluated in therapeutic intervention of infectious diseases. Here we describe a novel AMP, PXL150, which demonstrates in vitro a broad spectrum microbicidal action against both Gram-positive and Gram-negative bacteria, including resistant strains. The potent microbicidal activity and broad antibacterial spectrum of PXL150 were not associated with any hemolytic activity. Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) failed to develop resistance towards PXL150 during continued selection pressure. PXL150 caused a rapid depolarisation of cytoplasmic membrane of S. aureus, and dissipating membrane potential is likely one mechanism for PXL150 to kill its target bacteria. Studies in human cell lines indicated that PXL150 has anti-inflammatory properties, which might be of additional benefit. PXL150 demonstrated pronounced anti-infectious effect in an in vivo model of full thickness wounds infected with MRSA in rats and in an ex vivo model of pig skin infected with S. aureus. Subcutaneous or topical application of the peptide in rats did not lead to any adverse reactions. In conclusion, PXL150 may constitute a new therapeutic alternative for local treatment of infections, and further studies are warranted to evaluate the applicability of this AMP in clinical settings. © 2012 The Author(s).


Wiig M.E.,Uppsala University | Wiig M.E.,Uppsala University Hospital | Dahlin L.B.,Skåne University Hospital | Friden J.,Sahlgrenska University Hospital | And 4 more authors.
PLoS ONE | Year: 2014

Background: Postoperative adhesions constitute a substantial clinical problem in hand surgery. Fexor tendon injury and repair result in adhesion formation around the tendon, which restricts the gliding function of the tendon, leading to decreased digit mobility and impaired hand recovery. This study evaluated the efficacy and safety of the peptide PXL01 in preventing adhesions, and correspondingly improving hand function, in flexor tendon repair surgery.Methods: This prospective, randomised, double-blind trial included 138 patients admitted for flexor tendon repair surgery. PXL01 in carrier sodium hyaluronate or placebo was administered around the repaired tendon. Efficacy was assessed by total active motion of the injured finger, tip-to-crease distance, sensory function, tenolysis rate and grip strength, and safety parameters were followed, for 12 months post-surgery.Results: The most pronounced difference between the treatment groups was observed at 6 months post-surgery. At this timepoint, the total active motion of the distal finger joint was improved in the PXL01 group (60 vs. 41 degrees for PXL01 vs. placebo group, p= 0.016 in PPAS). The proportion of patients with excellent/good digit mobility was higher in the PXL01 group (61% vs. 38%, p=0.0499 in PPAS). Consistently, the PXL01 group presented improved tip-to-crease distance (5.0 vs. 15.5 mm for PXL01 vs. placebo group, p =0.048 in PPAS). Sensory evaluation showed that more patients in the PXL01 group felt the thinnest monofilaments (FAS: 74% vs. 35%, p=0.021; PPAS: 76% vs. 35%, p=0.016). At 12 months post-surgery, more patients in the placebo group were considered to benefit from tenolysis (30% vs. 12%, p =0.086 in PPAS). The treatment was safe, well tolerated, and did not increase the rate of tendon rupture.Conclusions: Treatment with PXL01 in sodium hyaluronate improves hand recovery after flexor tendon repair surgery. Further clinical trials are warranted to determine the most efficient dose and health economic benefits. © 2014 Wiig et al.


The present invention relates to pharmaceutical compositions enhancing the therapeutic effect of biologically active peptides, especially peptides derived from human lactoferrin. The compositions are useful for the treatment and/or prevention of wounds, scars, and post surgical adhesions.


Patent
Pergamum Ab | Date: 2012-01-25

The present invention relates to new peptides and to use thereof, in particular for treatment and/or prevention of infections, inflammations, pain, wounds, scar and/or tumours.


PubMed | Karolinska Institutet, Pharma Consulting Group Solutions AB, University of Southern Denmark, Sahlgrenska University Hospital and 3 more.
Type: Journal Article | Journal: PloS one | Year: 2014

Postoperative adhesions constitute a substantial clinical problem in hand surgery. Fexor tendon injury and repair result in adhesion formation around the tendon, which restricts the gliding function of the tendon, leading to decreased digit mobility and impaired hand recovery. This study evaluated the efficacy and safety of the peptide PXL01 in preventing adhesions, and correspondingly improving hand function, in flexor tendon repair surgery.This prospective, randomised, double-blind trial included 138 patients admitted for flexor tendon repair surgery. PXL01 in carrier sodium hyaluronate or placebo was administered around the repaired tendon. Efficacy was assessed by total active motion of the injured finger, tip-to-crease distance, sensory function, tenolysis rate and grip strength, and safety parameters were followed, for 12 months post-surgery.The most pronounced difference between the treatment groups was observed at 6 months post-surgery. At this timepoint, the total active motion of the distal finger joint was improved in the PXL01 group (60 vs. 41 degrees for PXL01 vs. placebo group, p=0.016 in PPAS). The proportion of patients with excellent/good digit mobility was higher in the PXL01 group (61% vs. 38%, p=0.0499 in PPAS). Consistently, the PXL01 group presented improved tip-to-crease distance (5.0 vs. 15.5 mm for PXL01 vs. placebo group, p=0.048 in PPAS). Sensory evaluation showed that more patients in the PXL01 group felt the thinnest monofilaments (FAS: 74% vs. 35%, p=0.021; PPAS: 76% vs. 35%, p=0.016). At 12 months post-surgery, more patients in the placebo group were considered to benefit from tenolysis (30% vs. 12%, p=0.086 in PPAS). The treatment was safe, well tolerated, and did not increase the rate of tendon rupture.Treatment with PXL01 in sodium hyaluronate improves hand recovery after flexor tendon repair surgery. Further clinical trials are warranted to determine the most efficient dose and health economic benefits.ClinicalTrials.gov NCT01022242; EU Clinical Trials 2009-012703-25.


Bacterial resistance against antibiotic treatment has become a major threat to public health. Antimicrobial peptides (AMPs) have emerged as promising alternative agents for treatment of infectious diseases. This study characterizes novel synthetic peptides sequentially derived from the AMP centrocin 1, isolated from the green sea urchin, for their applicability as anti-infective agents.The microbicidal effect of centrocin 1 heavy chain (CEN1 HC-Br), its debrominated analogue (CEN1 HC), the C-terminal truncated variants of both peptides, i.e. CEN1 HC-Br (1-20) and CEN1 HC (1-20), as well as the cysteine to serine substituted equivalent CEN1 HC (Ser) was evaluated using minimal microbicidal concentration assay. The anti-inflammatory properties were assessed by measuring the inhibition of secretion of pro-inflammatory cytokines. All the peptides tested exhibited marked microbicidal and anti-inflammatory properties. No difference in efficacy was seen comparing CEN1 HC-Br and CEN1 HC, while the brominated variant had higher cytotoxicity. C-terminal truncation of both peptides reduced salt-tolerability of the microbicidal effect as well as anti-inflammatory actions. Also, serine substitution of cysteine residue decreased the microbicidal effect. Thus, from the peptide variants tested, CEN1 HC showed the best efficacy and safety profile. Further, CEN1 HC significantly reduced bacterial counts in two different animal models of infected wounds, while Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) failed to develop resistance against this peptide under continued selection pressure. In summary, CEN1 HC appears a promising new antimicrobial agent, and clinical studies are warranted to evaluate the applicability of this AMP for local treatment of infections in man.


PubMed | Pergamum AB
Type: Journal Article | Journal: Applied microbiology and biotechnology | Year: 2013

Dramatic increase in bacterial resistance towards conventional antibiotics emphasises the importance to identify novel, more potent antimicrobial therapies. Antimicrobial peptides (AMPs) have emerged as a promising new group to be evaluated in therapeutic intervention of infectious diseases. Here we describe a novel AMP, PXL150, which demonstrates in vitro a broad spectrum microbicidal action against both Gram-positive and Gram-negative bacteria, including resistant strains. The potent microbicidal activity and broad antibacterial spectrum of PXL150 were not associated with any hemolytic activity. Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) failed to develop resistance towards PXL150 during continued selection pressure. PXL150 caused a rapid depolarisation of cytoplasmic membrane of S. aureus, and dissipating membrane potential is likely one mechanism for PXL150 to kill its target bacteria. Studies in human cell lines indicated that PXL150 has anti-inflammatory properties, which might be of additional benefit. PXL150 demonstrated pronounced anti-infectious effect in an in vivo model of full thickness wounds infected with MRSA in rats and in an ex vivo model of pig skin infected with S. aureus. Subcutaneous or topical application of the peptide in rats did not lead to any adverse reactions. In conclusion, PXL150 may constitute a new therapeutic alternative for local treatment of infections, and further studies are warranted to evaluate the applicability of this AMP in clinical settings.


News Article | November 7, 2016
Site: www.newsmaker.com.au

The report provides comprehensive information on the therapeutics under development for Venous Leg Ulcers (Crural ulcer)  ,complete with analysis by stage of development,drug target,mechanism of action (MoA),route of administration (RoA) and molecule type. The report also coversthe descriptive pharmacological action of the therapeutics,its complete research and development history and latest news and press releases. Additionally,the report provides an overview of key players involved in therapeutic development for Venous Leg Ulcers (Crural ulcer)     and features dormant and discontinued projects. The report helps in identifying and tracking emerging players in the market and their portfolios,enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage. Complete report on Venous Leg Ulcers (Crural ulcer)  - Pipeline Review, H2 2016 addition with 26 market data tables and 12 figures, spread across 71 pages is available at http://www.rnrmarketresearch.com/venous-leg-ulcers-crural-ulcer-pipeline-review-h2-2016-market-report.html This report features investigational drugs from across globe covering over 20 therapy areas and nearly 3,000 indications. The report is built using data and information sourced from Global Markets Direct's proprietary databases,company/university websites,clinical trial registries,conferences,SEC filings,investor presentations and featured press releases from company/university sites and industry-specific third party sources. Drug profiles featured in the report undergoes periodic review following a stringent set of processes to ensure that all the profiles are updated with the latest set of information. Additionally,various dynamic tracking processes ensure that the most recent developments are captured on a real time basis Biochaperone PDGF-BB, Cell Therapy to Activate Cathelicidin for Diabetic Foot Ulcers and Crural Ulcer, Cell Therapy to Activate VEGF for Venous Leg Ulcers and Diabetic Foot Ulcers, CL-05, CODA-001, CureXcell, CVBT-141B, Granexin , LL-37, NLP-328, PAC-G, RGN-137Stathmin-1, VF-001 Adocia, CardioVascular BioTherapeutics, CytoTools , FirstString Research, MacroCure Ltd, MediWound Ltd, NovaLead Pharma Pvt. Ltd, Pergamum , RegeneRx Biopharmaceuticals, Stratatech Corporation, Tissue Therapies Limited, Inquire before buying http://www.rnrmarketresearch.com/contacts/inquire-before-buying?rname=662437(This is a premium report price at US$2000 for a single user PDF license).

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