Details of Grant 

EPSRC Reference:	EP/Z002486/1
Title:	Peptide Manufacturing- Merrifield Synthesis 2.0
Principal Investigator:	Williams, Dr D
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department:	Chemical Engineering
Organisation:	Imperial College London
Scheme:	Standard Research - NR1
Starts:	01 October 2024	Ends:	30 September 2025	Value (£):	255,520
EPSRC Research Topic Classifications:	Manufacturing Machine & Plant
EPSRC Industrial Sector Classifications:	Manufacturing
Related Grants:
Panel History:
Summary on Grant Application Form
Peptide based drugs are one of the most important classes of new medicines. Peptides each containing a sequence of amino acids, the number and order of the amino acids in the peptide gives it unique biochemical properties. More than 7000 naturally occurring human peptides have been identified, and these often have crucial roles in human physiology, including actions as hormones, neurotransmitters, growth factors, ion channel ligands, or anti-infectives chemicals. The past 5 years has seen a rapid growth of new peptide drugs for diabetes which mimic a natural hormone called GLP. These new commercial drugs include Trulicity (Eli Lilly) and Ozempic(Novo-Nordisk) have become major drugs for managing type 2 diabetes. However, it has become clear in the past 12 months that these same drugs have major roles for controlling both obesity and heart disease, meaning that the demand and usage of these GLP mimics is likely to grow dramatically. However, the affordability of these new drugs is a serious issue, with annual costs for a patient is the USA using Trulicity is $10k. One significant factor in the cost of these peptide drugs is the complex process for their chemical synthesis which is specifically true for all therapeutic peptides than contain between 30 and 50 amino acids. The main method for synthesising peptide drugs is called the Merrifield Synthesis, which is commonly described also as solid phase peptide synthesis, and resulted in the awarding of the 1963 Nobel prize to Professor Merrifield. This technique has been improved incrementally over the past 60 years, but in remains unchanged at its core. The sequential growth, by chain elongation one amino acid at a time, of a peptide anchored to a solid resin particle. At the end of the synthesis, the final peptide is cleaved from the solid state media. It suffers from three primary disadvantages- it is not possible to synthesis peptides which are longer than 15 amino acids, the reaction process produces larges amounts waste chemicals, and it is not possible to synthesis non-linear peptides directly using this approach. The first two disadvantages directly contribute to expensive manufacturing costs, whilst the third disadvantage limited the ability of researchers to develop new non-linear peptide structures. The project will delivery key research data demonstrating a major advance in peptide synthesis developed by a UK university research group. We have developed a comprehensive improvement to the Merrifield synthesis approach, which we call Merrifield 2.0. This new method allows us to synthesis peptides of up to 50 amino acids directly using solid phase peptide synthesis and the method is much more sustainable; we anticipate reductions of up to 90% in waste products produced. These improvements will decrease manufacturing costs and also improve the sustainability of the entire peptide manufacturing process. In addition, this new synthetic approach allows us to synthesise for the first time a range of complex peptide structures, both linear and non-linear, which were not possible with the traditional Merrifield approach. This development in turn will open up new possibilities for pharmaceutical companies to develop new classes of peptide therapeutics, especially for oral delivery which is currently very difficult. The data generated in this project will allow us to quantify the process performance of our new manufacturing method, as well as confirming the purity and yield of the peptides we can manufacture. These data sets will be compared with data we will obtain using traditional synthesis methods. We will synthesis peptide materials at scales of 10 gm which to allow us to gain important industrial process data relevant to potential future scale up of our new manufacturing approach. In addition, we will demonstrate our ability to manufacture new peptide structures not currently possible using traditional synthesis approaches.
Key Findings
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Organisation Website:	http://www.imperial.ac.uk