Nanoenabled Peptide Pills - Unlocking the Potential of Therapeutic Peptides

Lead Research Organisation: University of Exeter
Department Name: Physics

Abstract

The poor bioavailability of peptides, nature's own 'drugs', limits their therapeutic application. The molecular envelope technology (MET) delivery platform allows their use as nano-enabled 'Peptide Pills'. The multi-disciplinary 'Peptide Pill' consortium, comprising drug delivery scientists, neuroscientists, physicists, chemical engineers and clinicians, will develop the pain peptide pill METDoloron. It is estimated that 20% of European adults suffer from chronic pain, which is often inadequately controlled by opioids. Additionally opioids can sometimes cause life threatening side effects. METDoloron avoids these problems by targeting a different receptor to currently used opioids, using an endogenous peptide derivative
and is therefore expected to have a significant impact on the large (US$ 50 billion), fragmented, and growing global market for pain therapeutics. The project partners will confirm METDoloron pharmacology, investigate nanoparticle transport mechanisms, establish scale-up and manufacturing processes, and confirm product (GLP) safety thus creating know-how in biophotonics, pain therapy, flow reactor design and nanoparticle processing techniques. First in man clinical trials will commence on conclusion of this project.

Planned Impact

OVERALL ECONOMIC AND QUALITY OF LIFE IMPACTS
The main output from this research is a set of protocols, data and materials which will lead to the first in human trials of METDoloron. The launch of METDoloron in Q3 2016 should contribute to the UK's economic competitiveness, as royalties will flow to Nanomerics. Additionally further academia/ business collaborations will follow once Nanomerics' MET technology has been validated in humans. With respect to quality of life improvements METDoloron is expected to provide improved pain therapy for some of the 80% of the world's population that has inadequate access to pain relief.

SPECIFIC PROJECT IMPACTS
In considering the individual work packages and the data that will emerge from the project over 2 years, the expected exploitable outputs arising from the research are as follows: 1) Confirmation of TPLENK/ delta opioid receptor as a drug/target combination, 2) Identification of MET nanoparticle transport mechanism, 3) Confirmation of regulatory strategy, 4) Definition of MET polymer, peptide and nanoparticle product specification, 5) Identification METDoloron CMC criteria 6) Flow process based optimised MET polymer synthesis method (Coflore ACR), 7) Demonstration of Coflore flow process
scale up (Coflore ATR), 8) Confirmation of METDoloron safety in two animal models (GLP standard), 9) Methods for cGMP manufacture and clinical outline protocol. These outputs will all impact on drug development, specifically unlocking further peptide and/ or neuroscience drugs for development, and demonstrate a path to translation.

SKILLS DEVELOPMENT
Staff recruited to the project will be working at the cutting edge of translational research and will develop the confidence to translate their own ideas into new therapeutics later on in their careers. Staff will benefit from working in close collaboration with Depomed and Nanomerics on the requirements for product selection. Staff, while acquiring further skills in their specialist area will also achieve an understanding of the requirements of other areas of the project (e.g. biophotonics staff will acquire knowledge of drug delivery and the reactor technician will gain knowledge of dosage form design requirements).

PATHWAYS TO IMPACT
Academic project partners, in consultation with the participating companies, will lead the dissemination of the science via high impact publications, peer group focused workshops (e.g. the February 2011 CARS workshop organised at Exeter University), conference presentations, and web sites (e.g. www.nanomedicines.org). In addition, the dissemination along commercial channels (e.g. partnering events) and knowledge transfer networks (e.g. NanoKTN) will be directed by the participating companies. Nanomerics' technology will profoundly benefit from the pre-clinical de-risking during the project as well as from the scheduled clinical follow-on development (see GANTT chart). Given Depomed's experience with their drug Gralise, the collaboration with our partner Depomed does provide a clear route for the clinical development, launch and marketing of METDoloron. The launch of METDoloron is planned for Q3 2016 following Phase I / II trials in 2014 and Phase III trials in 2015. Follow on products (e.g. TSB funded Anti-cancer Peptide Pill) would enter the market after that date.

Publications

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Cole M (2013) Microplastic ingestion by zooplankton. in Environmental science & technology

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Lalatsa A (2015) Chitosan amphiphile coating of peptide nanofibres reduces liver uptake and delivers the peptide to the brain on intravenous administration. in Journal of controlled release : official journal of the Controlled Release Society

 
Description The poor bioavailability of peptides, nature's own 'drugs', limits their therapeutic application. Molecular envelope technology (MET) delivery allows their use as nanoenabled medicines, with an up to 18-fold increase in brain levels. The multi-disciplinary 'Peptide Pill' consortium aimed to develop the pain peptide pill METDoloron. 20% of European adults suffer from chronic pain often inadequately controlled by opioids, which often have life threatening side effects. METDoloron avoids these problems by targeting a different receptor and using an endogenous peptide and is therefore expected to have a significant impact on the large (US$ 50 bn), fragmented, and growing pain market for pain.



This project confirmed pharmacology, investigated transport mechanisms, established scale-up and manufacturing processes, and confirmed product safety thus creating know-how in biophotonics, pain therapy, flow reactor design and nanoparticle processing techniques. It is anticipated that clinical trials will commence on project conclusion.
Exploitation Route The main output from this research is a set of protocols, data and materials that will lead to the first in human trials of molecular envelope technology for the delivery of peptides (MET Doloron). The launch of METDoloron, a new pain therapeutic with a better safety profile, should contribute to the UK's economic competitiveness, as royalties will flow to Nanomerics.



With respect to quality of life improvements METDoloron is expected to provide improved pain therapy, with fewer deleterious side effects for some of the 80% of the world's population that have inadequate access to pain relief.



The project also has indirect effects on UK R&D because of its strategic importance for the partnering companies. The project brought together the capabilities of two innovative technologies, Nanomerics' MET platform technology and AMT's Coflore system. Both enabling technologies with clear USPs and product profiles that make them attractive for their target markets. Nevertheless, significant market entry barriers existed for both novel technologies, in particular in the pharmaceutical industry. This project demonstrated the effectiveness of both technologies for this industry thus dramatically reducing market barriers and allowing the partner companies to attract further UK R&D investment for additional projects. To fully exploit the potential impacts of METDoloron, Nanomerics has entered into a mutually beneficial alliance with Depomed in order to progress METDoloron to clinical development. Depomed has product launch experience, having recently launched a neuropathic pain product, and have a marketing resource and a contracted sales force. To fully exploit the MET platform and generate partnering opportunities, Nanomerics will aggressively market its capability once each of the key validation steps has been reached, e.g. on achieving dosage form scale up, on filing an investigational new drug application and particularly once METDoloron has been validated in humans.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description The work carried out in EP/K502339/1 has supported a TSB project lead by Nanomerics Ltd for the development of a novel nanoparticle drug delivery system for enhancing the uptake of peptides into the brain. Label-free imaging (using techniques previously developed in EP/G061564/1) provided confirmation of particle delivery across the blood-brain-barrier to optimize the nanoparticle formulation and to provide mechanistic information required by the regulating bodies.
First Year Of Impact 2014
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description EPSRC Programme Grant
Amount £5,752,646 (GBP)
Funding ID EP/R020965/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 02/2018 
End 01/2023
 
Description EPSRC iCASE
Amount £75,000 (GBP)
Organisation University of Leeds 
Department Faculty of Engineering
Sector Academic/University
Country United Kingdom
Start 10/2015 
End 10/2019
 
Description The oral and intranasal delivery of 150 kDa antibodies
Amount £277,519 (GBP)
Funding ID EP/L024772/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 07/2014 
End 07/2017