Nanoenabled Peptide Pills - Unlocking the Potential of Therapeutic Peptides

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.

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 and will gain knowledge on the criteria for product selection. Staff, while acquiring further skills in their specialist area will also achieve an understanding 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 by Julian Moger), 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 between Nanomerics and 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.