Oncology Seminar at Australia House, London

The life sciences and healthcare networking organisation One Nucleus, which has over 500 member companies based mainly in London and the East of England, launched a successful series of day-long “leadership seminars” in important therapeutic areas in 2011.

Oncology has now featured in three of these including the very first, which was held in Clare College, Cambridge in May 2011.

The most recent oncology seminar in this mini-series, held 14th March 2012, had a slightly different focus from previous ones. It was co-sponsored by the state government of Queensland, Australia, and Queensland Trade & Investment and held in the splendid surroundings of Australia House in the Strand, London. 

This aimed to highlight both the importance of Australia (and particularly Queensland) in drug development and the growing reach of One Nucleus’ international collaborations.

The seminar was divided into three sections, only two of which had a specific focus on oncology. The first, introduced by Mario Pennisi, CEO of Life Sciences Queensland, provided a general introduction to that state as an environment for life sciences research and drug development. 

He highlighted Australia’s economic and political stability – it is the world’s twelfth largest economy, despite having only 0.33% of its population – and its well-developed framework for intellectual property.

Queensland, located in the north-eastern corner of Australia, is home to many world-class universities and public research institutes and a thriving commercial biotechnology sector.

Its whole life sciences sector has developed to take advantage of its tropical climate and rich biodiversity, attributes that are found in few highly developed and economically stable regions. 

Later in that session, Sue Lee from a specialist international courier company, World Courier, gave an interesting presentation about the challenges of setting up and running clinical trials in remote regions with often widely different climates. Australasia is now a popular location for clinical trials, particularly for diseases where there is an increased prevalence on the continent.

Malignant melanoma, particularly common in Caucasians who are regularly exposed to strong sunlight, is a classic example of this: figures from 2002 show age-standardised incidence rates for melanoma in Australia and New Zealand of 37.7 cases per 100,000 in males and 29.4 per 100,000 in females, both over twice the rates recorded in any other world region.

In its second and third sessions, the symposium moved away from a focus on Australia to discuss, first, new developments in technologies to enhance drug development in oncology, and, secondly, drug development partnership opportunities.

Jon Waterman-Smith, Business Development Director of PRECOS Pre-Clinical Oncology Services, introduced the second session by addressing the continuing need for technology innovation in oncology drug development.

He referred to the high failure rate of novel drugs in the clinic, citing a 2008 Lancet Oncology paper to say that 77% of the 800 candidate drugs that entered clinical trials for oncology indications between 1995 and 2007 had failed to reach the market and quipping that he “sounded like a broken record”.

Every step in the development of a novel cancer drug requires testing in validated, clinically relevant models of the tumour type involved.

Three presentations of novel technology developed in UK-based companies followed this introduction. Andrew McEwen of Quotient BioResearch described the use of a mass spectrometry technique, matrix-assisted laser desorption/ionization (MALDI), as an alternative imaging technique for in vivo studies of potential anti-cancer drugs.

Autoradiography has been used to track the distribution of a drug in animal tissue for many years. Ionisation using MALDI, which is a “soft” technique that keeps all molecules intact, allows drug molecules and any metabolites to be tracked after delivery, and it is particularly useful in visualising phospholipids. As an example, McEwen showed some stunningly clear images of tumours in mice treated with the tubulin-binding drug vinblastine as compared to control tumours.

Protein-protein interaction interfaces are theoretically useful but often technically intractable targets for drugs for cancer. Carol Austin, group leader for biology at chemistry-based drug discovery company, Selcia, described how capillary electrophoresis is being used with fragment-based screening to investigate this type of oncology target.

Fragment-based approaches rely on the fact that very small molecules that bind to drug target with low affinity can often be combined to form lead compounds, and these approaches have had some notable successes including the B-Raf inhibitor vemurafenib, recently approved for the treatment of melanoma. Fragment-based approaches do, however, have the disadvantage that fragment binding is low affinity and can only be detected using biophysical techniques.

Capillary electrophoresis has several advantages over other techniques such as X-ray crystallography for this; notably, it can be used with membrane-bound protein complexes and does not require either crystals or completely pure protein.

Martin Slater, Director of Consulting at Cresset Biomolecular Discovery, then gave an overview of his company’s molecular simulation software, focusing on a “more realistic” representation of the distribution of charge within molecules.

This session, focusing on technologies most appropriate in early-stage drug discovery, was followed by a series of presentations exploring opportunities for partnership in later-stage development.

Firstly, Charles Brigden, Licensing and Business Development Director of Amgen, described the prospects available for smaller companies wanting to work with his company, which with a current equity value of $54 billion has been described as “the world’s largest biotech”.

Amgen’s pipeline includes antibodies, peptides and small molecules targeted at many different cancer types; it currently has drugs in Phase III trials for difficult-to-treat tumours including ovarian, pancreatic and non-small-cell lung cancer.

Its recent acquisition of a German biotechnology company, Micromet, led to the incorporation of a promising monoclonal antibody in Phase II trials for leukaemia into its pipeline.

Amgen is seeking opportunities to license technologies and acquire molecules in many therapeutic areas, and has recently created a venture fund to support technologies that it considers too early-stage for licensing or acquisition.

Gaynor Fryers from AstraZeneca, speaking only days before disappointing Phase III results for the company’s candidate anti-depressant, TC-5214, were released, described her company’s emphasis on developing personalised healthcare: “the right products, in the right markets, for the right patients at the right time”.

Oncology is one of the first therapeutic areas in which the personalised approach is beginning to make a significant impact. AstraZeneca, like Amgen, takes a proactive approach to partnering and currently has over a thousand active partners located in many countries and covering many therapeutic areas. “We are looking for 40% of our drug development pipeline to be sourced from external alliances by 2014”, said Fryers. Another priority of AstraZeneca’s partnering programme is growing its international reach; it is building links with companies and research institutes in emerging economic areas, with a particular focus on China. Volitinib is a novel, selective inhibitor of c-Met tyrosine kinase that is being developed by AstraZeneca in partnership with Chi-Med (Hutchison MediPharma) in that country.

Finally, Victoria John, head of clinical partnerships at Cancer Research UK described opportunities for partnering with CRUK and its commercial development arm, Cancer Research technology.

One Nucleus and its predecessor networks, London Biotechnology Network and the East of England-based ERBI, have shown a serious commitment to promoting drug development for oncology, not least in its leadership seminar series. It will be interested to see how this programme develops in future years.