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A drug discovery success
Dear readers,
A CRO like BioFocus which engages in drug discovery for our clients has a number of success measures – some are financial - a profitable company is good for continuity and shareholders (Galapagos) and also good for the organizations with which we work – a financially stable organization gives comfort to both our suppliers and clients.
However, the success measure most interesting to our clients is the number and quality of candidate medicines that BioFocus delivers. We can now report on a major drug discovery success in which BioFocus has been engaged.
In November 2006, a new collaboration was publically revealed between BioFocus and the not-for-profit organization: Institute for One WorldHealth (iOWH). In this collaboration, iOWH engaged BioFocus to perform the chemistry, screening and ADME studies in a partnership to design, make and test compounds that would be a cure for diarrhea, particularly diarrhea caused by cholera toxin. The particular biological target, the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride ion channel found in the lung and gut. In the lung (and in defective form) the channel is responsible for cystic fibrosis. In the gut (and when over-activated by cholera toxin) it causes unregulated outflow of ions (and water) – an adult can lose 40L of water per day in some cases. Death – particularly of infants can occur within hours. Around two million people die from cholera-induced diarrhea every year.
With some early hit molecules emanating from the laboratories of UCSF (Professor A. Verkman) showing that the channel could be negatively modulated, the challenge was on to design and validate robust biochemical and cellular assays to evaluate compounds, and to turn the hit molecules into viable leads for progression to drugs. The ion channel biology expertise and a chemistry design team at BioFocus in Chesterford Park worked for three and a half years to generate molecules with in vivo activity and to get acceptable PK parameters. Many avenues were explored during the collaboration, including a very large HTS screen to search for new chemotypes. The work eventually revealed a clinical candidate iOWH032, a compound that has now gained IND approval for first-in-man administration. This was announced by iOWH on 1 March 2011.
This short article, by its size, cannot describe all the challenges that the teams had to overcome. BioFocus had to engage with many organizations besides iOWH – including the University of Pittsburgh in the USA and CROs in China. Some elements of the project have now been revealed, commencing with a poster presented by Kevin Doyle at the 21st International Symposium on Medicinal Chemistry in Brussels, Belgium, 5-9 September 2010. Details of the poster can be found on the iOWH website.
A lecture was given in India at the joint RSC/IICT conference in Hyderabad on 26 February 2011 by me. This presentation will be given again in the UK: first at the SCI sponsored “Young Chemist in Industry” meeting to be held in London on 9 May 2011 by Carrie-Anne Molyneaux and then at the 22nd East-of-England symposium on medicinal chemistry to be held in Hatfield on 19 May 2011 by Kevin Doyle.
The reception to the project success at the Hyderabad conference (India could of course be one of the major beneficiaries of this project) was incredibly supportive – I do not recollect BioFocus being named the “Mother Theresa of drug discovery”, before. Below is a picture of the author at the conference.
The iOWH provided coordination and direction from Eugenio de Hostos, Tue Nguyen and David Brown.
The BioFocus team was: Kevin Doyle, Graham Jones, Joanne Peach, Michael Russell, Stephen Penrose, Amanda Van de Poël, Carrie-Anne Molyneaux, Jackie Macritchie, Angus MacLeod, Sebastian Brückner, Joanne Shearer, David Cronk, Gary Clark, Alan Beresford, Ian Gowers, Simon Dowler, Richard Martin, Carmela Clark, Suzie Clarke, Scott Maidment and Matthew Gardener.
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Pictured at the joint RSC/IICT meeting held at NIPER and IICT in Hyderabad held 25-26 February 2011 are (left-to-right) Chris Newton, Professor Ray Jones (U Loughborough, UK), Dr David Alker (RSC), Professor Paul M O’Neill (U Liverpool, UK) and Dr Martin Drysdale (Beatson Institute for Cancer Research, Glasgow, UK).
Chris Newton
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