Development of epidermicin NI01 for nasal decolonization

Lead Research Organisation: University of Manchester
Department Name: Medical and Human Sciences

Abstract

The World Health Organisation have stated that infections caused by antibiotic resistant bacteria (e.g. MRSA) are one of the greatest current threats to public health and there is an urgent need for novel antibiotics to combat drug resistant infections. We have discovered epidermicin, an exciting and important new antibiotic that rapidly kills MRSA and other bacteria. The new antibiotic is more active than current antibiotics, is non-toxic and bacteria don't develop resistance to it. These are significant advantages over current antibiotics so we plan to develop epidermicin for clinical use. People who carry MRSA in the nose have a high risk of developing infection and transmitting MRSA, so we will examine how effective epidermicin is for removing MRSA from the nose. We will also carry out experiments designed to help us to understand how epidermicin kills bacteria and why they do not become resistant and carry out work to ensure that the antibiotic is not toxic when used clinically.

Publications

10 25 50
 
Description Demonstrated in a relevant model that epidermicin is better than the current therapy for preventing infection with methicillin resistant S aureus (MRSA), on of the most important pathogens seen in healthcare settings.
Determined the structure of epidermicin.
Identified novel data that supported submission (March 2014) of a second patent application protecting the technology being developed.
Exploitation Route In vivo data justify further development through the pre-clinical pathway towards nasal decolonisation, to prepare epidermicin for use in a Phase I clinical trial
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Findings from this work have been communicated to audiences in the general public (science in the news event and University of the 3rd Age meetings and in various local and national media outlets. The findings have been well received and generated interest in these settings.
First Year Of Impact 2013
Sector Healthcare
Impact Types Societal

 
Description Capital equipment for AMR research
Amount £142,000 (GBP)
Funding ID 86184-540263 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 01/2017 
End 03/2017
 
Description Health and Life Sciences call
Amount £933,000 (GBP)
Funding ID TS/R008396/1 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 08/2017 
End 07/2020
 
Description Industrial Biotechnology Catalyst - Industry Research award
Amount £417,092 (GBP)
Funding ID 44921-302214 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 04/2015 
End 03/2017
 
Description Pre-clinical validation of a potent candidate in the fight against AMR HCAI
Amount £1,182,041 (GBP)
Funding ID 971631 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 02/2019 
End 01/2021
 
Description SfAM PhD
Amount £67,000 (GBP)
Organisation Society for Applied Microbiology 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2017 
End 09/2020
 
Description Development of expression system for commercial scale production 
Organisation Ingenza Ltd
Country United Kingdom 
Sector Private 
PI Contribution Ingenza have partnered with us to develop the recombinant expression system for production of epidermicin and related peptides. This work is now supported by a TSB/Innovate UK IBC award (starting April 2015). My research team will be evaluating the peptides that are produced in the Ingenza expression pipeline.
Collaborator Contribution Ingenza are bringing 14 years of IB expertise to the project to maximise the chance of successfully achieving our target level of expression
Impact None yet
Start Year 2014
 
Description Mode of action work with Leeds University 
Organisation University of Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution Peptide supplied to Alex O'Neill who worked with Post-doc on project and his own PhD student to investigate the mode of action
Collaborator Contribution Investigated the mode of action using liposomes and in house strains of bacteria to indicate cell wall activity of peptide. Also mapped the cellular response at the level of macromolecular synthesis
Impact Poster presentation at ICAAC, 2013. This work is being written up into a manuscript for submission in the near future
Start Year 2012
 
Description National Physical Laboratory/IBM for creation of novel antimicrobials based on epidermicin 
Organisation National Physical Laboratory
Country United Kingdom 
Sector Academic/University 
PI Contribution This is part of a new Innovate UK funded project with NPL, the University of Plymouth and Ingenza Ltd. Our role in the project is to guide design of new antimicrobials based on epidermicin and investigate the activity of variants. This will include assessment of spectrum of antimicrobial activity against clinically relevant bacteria and investigation of toxicity of novel antimicrobials.
Collaborator Contribution Max Ryadnov at NPL has been working with colleagues at IBM Hartree to develop novel epidermicin variants, using cognitive computing. The NPL/IBM approaches will provide new sequence variants that will be investigated in silico at IBM. Promising molecules will be synthesised at NPL and initial bioactivity assessments will be carried out. Promising candidates will be passed to my group for further testing (above). Any candidates worth progressing to larger scale evaluation will be passed to Ingenza for recombinant expression process development and scaleup.
Impact This collaboration was cemented and current work facilitated by an award from Innovate UK (Health and Life Sciences award)
Start Year 2017
 
Description Wound healing activity of epidermcin 
Organisation Roskilde University
Country Denmark 
Sector Academic/University 
PI Contribution Discussions we held at the International Antimicrobial Peptide meeting in Leiptzig, Germany in August 2016 about using epidermicin in Havard Jenssen's wound healing assays. An MTA was put in place and epidermicin was sent to Roskilde for use in assays.
Collaborator Contribution The epidermicin provided was used in wound healing and preliminary cytokine assays
Impact An out line patent application has been submitted based on this work and Michelle Vang from Havard Jenssen's group is planning a 3 month visit to the UK to work in my lab to develop the data set further, to support a future grant application.
Start Year 2017
 
Title NOVEL ANTIMICROBIAL PEPTIDES 
Description The present invention provides novel antimicrobial peptides and nucleic acids encoding them, the peptides having an inhibitory or bactericidal/bacteriostatic effect on both Gram- negative and Gram-positive bacteria. The invention includes methods of treating bacterial infections and preventing the spread of the infections or contamination by the infection. The peptides of the present invention are of particular use as therapeutics to treat Gram- negative infections and are of use in impregnation, covering or coating medical devices or implants or prosthetics prior to introduction into a patient's body 
IP Reference WO2015132572 
Protection Patent application published
Year Protection Granted 2015
Licensed No
Impact None yet
 
Title Epidermicin 
Description Pre-clinical development of epidermicin towards use in nasal decolonisation for MRSA carriage - during the FoF project we obtained excellent in vivo data in a murine model relevant to the selected clinical indication. This has supported further funding applications to facilitate development of epidermicin towards clinical trials 
Type Therapeutic Intervention - Drug
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2014
Development Status Under active development/distribution
Impact We solved the crystal structure of epidermicin. This will inform future development and inform our efforts to understand the mode of action. 
 
Company Name AMPROLOGIX LIMITED 
Description A University of Plymouth spin out established to commercialize epidermicin IPR arising from work in University of Manchester and University of Plymouth. 
Year Established 2018 
Impact Shortly after company formation, an award was made from the Department of Health and Social Care (via Innovate UK/SBRI) for a contract valued at £12.m to progress the lead compound (epidermicin) through pre-clinical development.
 
Description Haliwell paper Press Release 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A press release was issued by the University of Plymouth in February 2017 to promote the publication of a paper describing unique and potent activity of epidermicin in an animal infection model. This release was picked up locally by Radio Devon featuring on the local eveing news (http://www.bbc.co.uk/news/live/uk-england-devon-38929340). A number of phone calls were taken as follow up to the release.
Year(s) Of Engagement Activity 2017
URL http://www.bbc.co.uk/news/live/uk-england-devon-38929340
 
Description Opinion piece in local print news 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact Opinion piece drafted and submitted to regular media outlets. This article aimed to increase awareness about antibiotic resistance during World Antibiotic Awareness week in November 2017 and mentioned briefly the work in my group developing new antibiotics. The story was picked up by the Cornish Times and I was subsequently approached by the Mail on Sunday for comment and input into a short piece on the health related importance of marine environments (this was around the time BBC were showing the Blue Planet series.
Year(s) Of Engagement Activity 2017
URL http://www.cornish-times.co.uk/article.cfm?id=112541&headline=World%20Antibiotic%20Awareness%20Week&...
 
Description Press release on company formation 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A press release from the University of Plymouth was made to publicize the formation of Amprologix Ltd. This was coordinated with releases from Ingenza (industrial partners) and a 'reach' article by Frontier IP ltd, the University of Plymouth commercialisation partners, who have an equity share in Amprologix. This story was picked up by various local media outlets and international business sites. The release and a subsequent one about award of an SBRI contract (971631) generated interest in academic an industry quarters and resulted in invites to present at Bioinfect, Manchester Nov 2018 and the conference on Novel Antimicrobials and AMR Diagnostics, Berlin, March 2019. It also resulted in many offers of service provision etc to assist with company development or R&D.

Examples of relevant sites referencing the original release -

https://cen.acs.org/pharmaceuticals/antibiotics/UK-antibiotics-firm-Amprologix-launches/96/i39
http://www.pharmtech.com/amprologix-ingenza-get-funding-antibiotic-development
https://www.bloomberg.com/research/stocks/private/snapshot.asp?privcapId=588605641
Year(s) Of Engagement Activity 2018
URL https://www.plymouth.ac.uk/news/university-spinout-company-to-develop-new-antibiotics
 
Description TEDx Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Based on my expertise and profile in antibiotic resistance and discovery (from UKRI funded research), I was invited to present a TEDx talk. This talk has now had nearly 2000 views on Youtube since January 2019.
Year(s) Of Engagement Activity 2018
URL https://www.youtube.com/watch?v=makV286ZFDk&t=11s