Innovations pubs.acs.org/acsmedchemlett
Cite This: ACS Med. Chem. Lett. XXXX, XXX, XXX−XXX
Closing the Loop: Developing an Integrated Design, Make, and Test Platform for Discovery David M. Parry*,†
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Cyclofluidic Ltd., BioPark, Broadwater Road, Welwyn Garden City AL7 3AX, U.K. ABSTRACT: The relatively slow cycle time within medicinal chemistry from synthesis to assay is constantly being challenged to help improve the efficiency of the discovery process. While both synthesis and assay have been automated to varying degrees, there has, until recently, been limited focus on the complete design, make, and test process. This Innovations article outlines the development of Cyclofluidic from inception through to the commercialization of a fully integrated closed loop design, synthesis, and screen platform. KEYWORDS: Automated Discovery, Design Make and Test, Integration, Flow Synthesis, ABL1 Kinase
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involvement being only later in 2008 amid changes within UCB that I successfully applied for a position within Cyclofluidic and joined at the beginning of 2009 as the first employee. Starting out at the helm of a new company on day one is both incredibly exciting and daunting in equal measure. The challenges were numerous, while both a business and technical plan were in place as part of the funding process that still left many open questions. I was very comfortable with the scientific and technical aspects to be undertaken having been increasingly involved with the evolution of the proposal but may have taken a slightly different stance on some of the more challenging technical milestones had I known I was going to be responsible for their delivery. Running a business from day one, however, was an entirely new challenge! Company location, suitable facilities, and how best to identify and recruit staff were very much at the top of the list alongside the more mundane but no less important business related aspects including insurance, solicitors, accountants, etc. A career to date in a research environment did ensure that I was well equipped to find answers to the questions and rapidly move the business forward. The business plan was to undertake a research and development program to build the platform (later to be christened CyclOpsCyclofluidic Optimisation Platform) and then to move to revenue generation through the sale of hardware. The investors had certain preferential rights in terms of both technology access and purchase. The first challenge was to assemble a suitable team with the breadth of skills required to deliver on the business plan. A very wide range of expertise was required from synthetic chemistry ideally with flow experience, biochemistry and assay
ne of the highlights of working as a medicinal chemist is receiving the latest set of biological data associated with both new and existing compounds. Did the structure−activity relationship (SAR) continue to hold up as expected? Are there new trends emerging? Which compounds are suitable for further investigation and how is the latest data going to influence the design of future compounds? It is this constant feedback of data for new molecules that satiates the appetite of the medicinal chemist ultimately resulting in new compounds entering into the clinic. Frustratingly, the lag between synthesis and assay results was and still is frequently measured in weeks. It was during early 2007 that an intriguing proposition was being circulated around pharma companies to build a Design Make Test platform for small molecule discovery that would slash the cycle time of days and weeks to just hours. It would be achieved through setting up and financing a new company to undertake the technology development and build a fully integrated “closed loop” platform encompassing the design, synthesis, and assay of new molecules with immediate feedback of the results into the next design cycle−closing the loop. The company would be able to build on the pioneering work1 undertaken by the GSK technology development department in the UK under Brian Warrington’s direction. A significant incentive was the benefit of potential eligibility for a grant from the UK government, which would provide support for a collaborative project in the areas of microfluidics and life sciences and derisk the partners investment. While there was initial interest from a large number of potential participants in the project, it was only UCB and Pfizer who signed up to the 5 year staged equity investment in 2008 to initiate the project. This met the collaborative requirements of the UK DTI (later to become InnovateUK), Cyclofluidic was incorporated, and the grant was secured in the summer of 2008. Up until this point my role had been to champion the proposal and gain management support for the investment within UCB; I had not foreseen my personal future © XXXX American Chemical Society
Received: March 8, 2019 Accepted: May 6, 2019
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DOI: 10.1021/acsmedchemlett.9b00095 ACS Med. Chem. Lett. XXXX, XXX, XXX−XXX
ACS Medicinal Chemistry Letters
Innovations
reaction tube at a defined rate with heating and cooling options. It was quickly agreed that using a commercial product was the most effective use of the internal resources rather than trying to “re-invent” and build from scratch. This strategy of utilizing existing hardware where available and innovating when required became a core strategy for the company; with the advantage of vendor maintenance and software support. The scale of synthesis was an important consideration for the project; the technical plan foresaw a microfluidic scale platform (a strict definition of microfluidic is still elusive; however, diameters of
