Academic-industrial collaborations make their mark in early drug discovery.

The general public might associate drug discovery research with a handful of large pharmaceutical and perhaps biotech companies, but there is also a great deal of pertinent activity that takes place within universities around the world. Occasionally, this may reach the headlines, as with the recent story concerning a potential treatment for malaria, whose development was led by the Drug Discovery Unit at the University of Dundee in Scotland. However, it is only in a few academic institutions, such as Dundee, that a reasonably complete complement of drug discovery capabilities exists. More commonly, university groups are strong in fundamental biology and identifying potentially novel targets for drug discovery projects, but lack experience in translating these opportunities into candidate drug molecules and ultimately into clinical trials.

Realising this, the Wellcome Trust, one of the world’s largest charitable foundations dedicated to improving health, initiated the Seeding Drug Discovery (SDD) initiative in 2005 with the stated aim of developing “drug-like, small molecules that will be the springboard for further research and development by the biotechnology and pharmaceutical industry in areas of unmet medical need.” Although not restricted to university groups, many of the SDD-funded programmes bring academics together with experienced drug discovery teams from contract research organisations (CROs). In this way, the novel biological insights from academia can be combined with industry-seasoned medicinal chemistry to yield a potentially winning combination.

Some examples of CRO-academic collaborations funded by the SDD initiative include:

  • Sygnature Discovery and Kings College London whose partnership sought new treatments for Alzheimer’s disease. This collaboration led to the formation of a spin-out company called CoCo Therapeutics in 2013.
  • Domainex and St George’s, University of London and the University of Manchester working together to explore a new class of experimental drugs that block the trigger of allergic reactions, including asthma.

Charles River has been involved in the SDD scheme since its inception and continues actively to engage with academic groups around the world who are involved in drug discovery. One of the earliest SDD-funded collaborations in which CRL was engaged was with the University of Edinburgh in Scotland. This project commenced in 2005 and sought to discover a novel treatment for cognitive impairment by targeting an enzyme known as 11-β hydroxysteroid dehydrogenase-1 (11β-HSD1), normally associated with metabolic, rather than neurological, disorders.

The rationale for this approach is that, in response to stress, a hormone known as cortisone is released by the adrenal glands. Cortisone affects certain areas of the brain, particularly the hippocampus, where 11β-HSD1 catalyses the conversion of cortisone to its active form, cortisol. Cortisol binds to glucocorticoid receptors and amplifies the stress response. It is believed that chronic stress and high cortisol levels lead to formation of amyloid plaques and neural death resulting in cognitive impairment. By blocking the action of 11β-HSD1, the production of cortisol can be reduced, mitigating the effects of stress.

Between 2005 and 2010, CRL and the university worked together on the project. CRL provided all the medicinal and synthetic chemistry support for the project, generating over 1000 compounds for biological testing at Edinburgh. The inventive contributions of CRL scientists are recognised by their names being included as inventors on the patents associated with the project. CRL also supplied vital in vitro ADME and in vivo PK data to help guide the medicinal chemistry effort, resulting in the design of compounds with improved metabolic stability. [1]

The result of this combined endeavour was a drug candidate known as UE2343. This compound successfully completed Phase I clinical trials in 2013 and was subsequently licensed in 2014 to an Australian company called Actinogen. UE2343 is now branded as Xanamem™ and is expected to move into a Phase II trial in patients suffering with mild cognitive impairment later in 2015.

The discovery of Xanamem™ represents a validation of the vision of the Wellcome Trust for the SDD initiative. In addition, it provides a compelling example of the potential of academic-industrial collaboration to bring together the “best of both worlds” with the aim of delivering improved drug treatments for patients.

Citations

  1. Webster, S. P.; Binnie, M.; McConnell, K. M. M.; Sooy, K.; Ward, P.; Greaney, M. F.; Vinter, A.; Pallin, T. D.; Dyke, H. J.; Gill, M. I. A.; Warner, I.; Seckl, J. R.; Walker, B. R. Modulation of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity by 1,5-Substituted 1H-Tetrazoles., BioOrganic and Medicinal Chemistry Letters, 2010, 20, 3265-3271.

How to Cite

Clark, David E., The Best of Both Worlds. Eureka blog. Jul 8, 2015. Available: http://eureka.criver.com/the-best-of-both-worlds/