GHP January 2016

ghp January 2016 | 27 innovation & technology There’s no shortage of headlines or catchy programme titles: the ‘Antibiotic Apocalypse’ is coming; the world is on the ‘Cusp of the post-antibiotic era’; ‘Fears grow over increased antibiotic resistance’, to take three from BBC news features this year. There are warnings going back several years from top politicians including Prime Minister, David Cameron, and government scientific advisers with top level reports and a UK antimicrobial resistance strategy (2013 – 2018). In the modern media-driven world, all these things might suggest quick action and rapid results. However providing the world with a new generation of effective anti-infective drugs for bacterial, parasitic, fungal, and viral infections is a huge problem with many dimensions. A BBC radio series (March 2015) was entitled ‘Restarting the antibiotic pipeline’ so it’s fair to ask whether there are indeed appropriate starting points now; are there new antibiotics entering the pipeline? Certainly there are many candidates reaching phase 1 and phase 2 clinical trials. Traditional sources of new compounds, natural products and chemical synthesis, are still providing active molecules. Bacteria themselves continue to be a source; discoveries at Northeastern University in the USA have been labelled ‘Game-changers’ for medicine in headlines; using new technologies for screening the products of previously undescribed bacteria, a new antibiotic called teixobac- tin has been discovered and is being taken forward to development. Chemical synthesis also continues to provide new candidates. In the UK, Summit Thera- peutics has a new compound with a new mechanism of action specific for Clostridium difficile infections; it is now in phase 2 clinical trials. This compound is a competitor for one of our candidate antibiotics discovered at the University of Strathclyde. We have a compound with a broad anti-Gram-positive bacterial spectrum of activity but formulated for C. difficile in- fections successfully completing phase 1 clinical trials carried out by our partner company, MGB Biopharma. A distinctive feature of our work is that our compound platform provides compounds that we can tailor to be effective against different infective agents. Currently in addition to the highly active compound in clinical tri- als, we are developing compounds for Gram-negative infections, for tuberculosis, and for parasitic infec- tions. In the last case, we are especially interested in African animal trypanosomiasis, for which we have compounds that are effective in mouse models of this disease of cattle. The impact of good and well-man- aged veterinary medical products must not be ignored despite the natural focus on human medicine. No doubt more candidates will continue to come forward but there is a downstream problem, namely taking compounds from phase 2 to the market. For example, until very recently a new peptidomimetic compound specific for challenging Pseudomas aerug- inosa infections was being developed by Polyphor with a partnership agreement with Roche for a phase 2 study. Roche pulled out. This is just one expression of the problems that big pharma has with antibiotics. The current commercial model for drug marketing does not work in terms of providing what they would regard as an adequate return. With this in mind, both Astra Zeneca’s and Glaxo SmithKline’s senior manage- ment have publicly urged the establishment of a new commercial model. As a scientist who works at the input to the pipe- line, I’m not well qualified to know what this model should be. On the other hand, as a recent member of the Scottish Medicines Consortium with a personal responsibility for representing the patient and public interest, I’m seriously concerned that the commercial drive is not the only consideration. A world without antibiotics is a public health issue and avoiding the apocaplypse needs the public interest at its heart. This picture shows the ideas behind our new drugs. The stick molecules are binding to the minor groove of DNA These pictures show our drug that has now passed phase 1 clinical trials. Left: MGB-BP3 formulated in capsules for treating Clostridium difficile. Right: a freeze-dried sample of MGB-BP3 for reconstitution as an intravenous medicine (courtesy MGB Biopharma).